I Was Considered A Nobody

[MUSIC PLAYING] FLORA LICHTMAN: Hi. Flora here. We have something really special on the podcast for you today. This is a labor of love for me. It’s an audio series I worked on before I came to Science Friday. I made it with the Hypothesis Fund, a science philanthropy that enables scientists to pursue their boldest ideas. And that’s what this series is all about.

Each episode is an intimate profile of a scientist who was, or in some cases, is, out on a limb, pursuing their most daring idea, even if it’s risky or unpopular, or, in the case of today’s episode, gets them laughed out of a room. But here’s the thing– sometimes those bold ideas can change the world. You’re the first to hear this, and I hope you enjoy it.

I want to introduce you to a scientist who spent most of her career in complete obscurity. She was a biochemist at the University of Pennsylvania.

KATALIN KARAKO: I know that Penn is a very prestigious place. But I was considered nobody there.

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They thought that I am crazy. They questioned my quality as a scientist.

FLORA LICHTMAN: She never ran her own lab, no tenure track. At one point, she was demoted. She got one grant ever.

KATALIN KARAKO: Listen, I was working there 24 years. I never gave a lecture.

FLORA LICHTMAN: She held on to her job by a thread until one day she walked into work and found her rolly chair, her notebooks, her lab equipment in the hallway. A lab tech was throwing the remainder of her stuff in the garbage can.

KATALIN KARAKO: So I was just like, what’s going on here? And she said that you have to talk to the chairman.

FLORA LICHTMAN: That was it. She was being forced out. She told her chairman he was making a huge mistake, that what she was doing in that lab would change the world someday.

KATALIN KARAKO: I literally told the chairman, this place will be a museum.

FLORA LICHTMAN: You told him it’d be a museum. That’s an amazing thing to say when you’re being basically kicked out of your job.

KATALIN KARAKO: Yes, because I believe so much that one day, it will be important.

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FLORA LICHTMAN: And here’s the craziest part about this story. She was right. That was Katalin Kariko. You may recognize the name because 10 years after her stuff was being dumped in the trash, she was on a stage in Stockholm.

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– I invite you now to step forward to receive the Nobel Prize.

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– It’s crazy. It’s just so unlikely.

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FLORA LICHTMAN: This is David Langer. He’s an old friend and colleague of Katalin Kariko’s. Most people call her Kati. He calls her Kate.

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– Well, Kate is probably the first Nobel Prize winner that wasn’t a professor. It’s this weird thing of someone who’s completely out of left field who achieves the greatest accomplishment in science and saved the world. It’s like, are you kidding me?

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FLORA LICHTMAN: This research that other scientists had dismissed for decades changed everyone’s life on this planet.

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– It led to the frickin’ COVID vaccine. I mean, if you look at all the other Nobel Prize winners ever, no one has a story like Kate.

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FLORA LICHTMAN: This is The Leap, a new show about gutsy scientists who have risked their careers, their reputations, and even their lives to make a breakthrough.

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– Hello, girls. Oh, this is for me, oh.

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FLORA LICHTMAN: Producer Annette Heist and I went to Kati’s house to talk to her. She greeted us at the door, warm and welcoming, no shoes on. And she immediately put the flowers we brought in water.

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– Oh, you are so kind. Thank you.

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FLORA LICHTMAN: And then she took us to her office. And the first thing you notice when you walk in are two walls lined with glass cabinets.

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– My husband did the, ‘kay, you know… this one also.

– Did he build it?

– Yeah, everything. Even this one.

– Oh, wow.

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FLORA LICHTMAN: Kati’s husband built these cabinets to hold the most science bling I have ever seen in my life– dozens and dozens of gilded metals, embossed coins, shiny statuettes.

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– Yeah, that stuff, Alfred Nobel Prize here.

– This is wild. I feel like I’m in a museum.

– Yeah.

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FLORA LICHTMAN: We sit down and Kati introduces herself. And you’ll notice, she doesn’t mention the prizes, or really even much about her work.

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– I am Katalin Kariko, and I am a scientist, a biochemist by training. I am Hungarian and also US citizen. And I came to this country in 1985. Prior to that, I lived in Hungary. And I was very happy there. Now I am very happy here. I have a wonderful husband for 44 years– 44.

FLORA LICHTMAN: The only bragging she eventually gets to is about her daughter.

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– And then I have a daughter, Susan Francia. And she’s a two-time Olympic champion, five-times world champion. I was very proud of her always. Yes. And I have two grandchildren.

– I feel bad for those grandkids– a grandmother who has a Nobel Prize, a mother who’s an Olympic medalist. It’s a lot of pressure.

– They will handle.

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FLORA LICHTMAN: Kati’s rise to science superstardom is surprising in a lot of ways, including where her story begins. Kati grew up in a humble place, a town in rural Communist Hungary.

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– We lived in this very small adobe house with a red roof. And we had animals, chickens, pigs, and cats. And we play mostly on the street. The street was dirt road. And maybe once a week, we have seen a car. Life was so simple.

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– Kati’s mom was a bookkeeper. Her father was a butcher. Neither had gotten much of a formal education, but they made sure their kids did. And from a young age, Kati loved biology.

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– I was not the average kind of person. In elementary school, I already was competing in biology, and I get third best in the country. And it was a whole week competition Can you imagine? For elementary school children, for a whole week.

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FLORA LICHTMAN: Kati found her own path to science. She didn’t come from a long line of scientists. She wasn’t pressured to be a doctor. She just loved biology and was determined to study it. She went to university and then graduate school. During that time, she met her future husband, Bela Francia, and later gave birth to their daughter Susan. And just like with science, Kati did motherhood on her own terms.

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– When mine was born, my first day, I talked to her like a real person. I introduced myself. Hi, [SPEAKING HUNGARIAN], my name is– I said my name, and I said, I am your mother. And she wanted to hear the story many, many times because I introduced myself to my own child. But this happened. This was real.

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FLORA LICHTMAN: Within three months of that moment, Kati was back in the lab, working on RNA, the family of molecules she’d devote her career to and that would later bring her to that award stage in Stockholm.

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RNA is in all living cells and works alongside DNA. So DNA holds the instruction manual to build and maintain the body. And RNA is kind of like the middle manager that takes those directives and turns them into action items for the team. There are different RNAs, but Kati focused on messenger RNA, mRNA. Its job is to carry instructions to factories in the cells that use those instructions to churn out proteins.

That’s all just basic biology. But here’s where Kati followed her intuition again. She thought we should be able to harness mRNA, to use it, to direct cells to manufacture beneficial proteins, like proteins that would help us build immunity or help break up clots. To Kati, mRNA seemed like a potentially paradigm-shifting medical tool, but most people thought this was a complete pipette dream.

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– I have to say that when I mentioned to somebody that I make mRNA and I work with it, they usually felt sorry if they were sympathetic. Or if they’re less sympathetic, they thought that I am crazy.

– It was so disruptive to the conventional wisdom.

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FLORA LICHTMAN: Here’s David Langer again. He worked with Kati in these early days as a student. And he saw firsthand what she was up against.

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– There’s just basically bias against it. The reason is because there are naysayers, which is the enzyme that basically breaks RNA down. They’re all over the labs, and they’re all over the body. And they’re everywhere.

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FLORA LICHTMAN: The problem with RNA is that it’s unstable. It breaks down easily. And the prevailing view was that working with it in the lab, keeping it on a shelf, getting it into a cell, all that was basically impossible. But Kati didn’t really care about the prevailing view, and she was not scared off. She looked at these issues and said, these are just problems that I can solve with the right techniques.

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– For example, I never wear gloves because what I realized that people were wearing gloves, they think that, OK, and then they are touching their forehead. They’re touching something. And now it is– the RNA is there. But one, I know that I don’t have gloves, I work carefully.

– You’re aware. You’re more aware.

– Yes, more aware. Because every miniature things, there’s good laboratory practice. I always said, that’s what you have to do.

– Kate used to be crazy about cleaning all the glassware, for example. How to wash your freaking beakers, that’s how you micro she was. She taught me that, to clean a beaker correctly, don’t fill the whole thing up. You only fill it up a third of the way and swirl it around twice. It’s much better than once, because the water coats the– this is the kind of crap she was doing. And it’s like, I still think of that. When I’m rinsing out a cup, I never rinse it, fill it up the whole way. You just fill up the bottom third. That was Kate Kariko.

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FLORA LICHTMAN: The other thing is that Kati is brilliant at experimental design. Solving these little puzzles and looking for clues was all part of the fun. And she looked for inspiration everywhere– academic journals, historical, scientific accounts, Law and Order.

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– I like to watch the real crime investigation just to understand the logic. When you have absolutely no clue what kind of thinking you need to find the perpetrator and what logic you use. And this is like, we are investigators, scientific investigators. And this little thing, which somehow doesn’t fit, that will lead us to the right answers.

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FLORA LICHTMAN: Kati was always open to letting the data lead her to the truth.

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– I wanted always to poke holes, not to prove it, but disprove–

– Disprove your idea.

– Yeah.

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because science should be about the truth.

– That’s Kate’s strength. And the truth is, that’s rare. You want to be right so badly because a lot of scientists have a motivation to get granted or to make money. They tend to take their data and prove themselves right. In other words, if you do an experiment and the data doesn’t confirming your hypothesis, then maybe the experiment must be wrong. Rather than taking the data and saying, hey, this is interesting. Even though I wasn’t right, what’s the reason for this?

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FLORA LICHTMAN: That is how Kati approached her research. She was focused on truth seeking above all else, which is a noble attribute that came with some serious liabilities. And it may help explain why she was demoted and later forced out of Penn. Because while some scientists focus their energy on building their career, publishing, networking, glad handing the right people, Kati almost seemed allergic to any kind of wheel-greasing.

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– She was never afraid to say, that person’s a complete idiot, even if they were someone who everyone thinks is God’s gift to whatever, to medicine. And this would get around.

– To excel in science, you have to be agreeable when you 100% not agree, to this kissing up and things like that to advance in department or some kind of promotion. So many people emphasized that, and then they say that it is everywhere.

– You didn’t do that, though.

– No, no. That’s why I couldn’t advance there.

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FLORA LICHTMAN: But Kati says it didn’t matter to her because the lab was her happy place.

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– I did not care that I was there all weekends and working so long. I hardly can wait in the morning to go to work. Because you have to solve so many problems. And that’s what science is all about, figuring out something. Oh, this is what’s going on.

– You just wanted to be in the lab making discoveries.

– Yes. I remember every little technical thing, like purifying long RNA, realizing that nobody ever published on it and coming up with different ideas. And then I just wanted to test out. I cannot imagine any other job that would give you that kind of happiness.

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FLORA LICHTMAN: A turning point came in 1997. Kati was waiting to use the copy machine at Penn and met an immunologist named Drew Weissman. Kati was in the habit of talking up mRNA’s therapeutic potential to anybody who’d listen, and Drew was intrigued. They decided to work together to make an mRNA vaccine.

They started with HIV, because that’s what Drew was working on. And here’s the basic idea. Vaccines introduced the body to a harmless version of a pathogen so your immune system can quickly recognize and attack the real version if you get infected. So Kati had to cook up the mRNA to carry instructions for a piece of the virus. Then they had to get that mRNA into cells, and then they had to get the cellular factories to use that mRNA to churn out bits of virus.

These viral proteins prepare the immune system to recognize the real virus if it comes along. So they did all that. And then they hit a huge roadblock. Their mRNA was causing inflammation. Now, inflammation can kill people. So if mRNA was going to be used for medicine, this problem had to be solved. And while other people might say, oh, I guess we’re done, let’s go on to something else, Kati saw this as just the next challenge to work through.

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– She knew she was going to make it work. It was just a puzzle she had to solve. And as long as she could keep the lights on, she was going to solve the problem. And what’s amazing is she did solve the problem, and nobody cared.

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FLORA LICHTMAN: This is an amazing wrinkle to the story. So in 2005, after years of work, Kati and Drew finally solved the inflammation problem. They figured out how to engineer mRNA in a brand new way so that it didn’t trigger inflammation. It was a huge breakthrough, and they were waiting for the red carpet to be rolled out. But instead, they got this.

[CRICKETS CHIRPING]

The research ended up in a smaller journal called Immunity, because when they brought it to the big, top-tier journals, it was rejected.

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– The science was not open to this. Even after they published the paper, nobody cared about it. It’s just incredible.

– This is the thing that I don’t understand. Why did nobody, especially after that paper, why did nobody care?

– I think that there’s a conventional wisdom that exists, and it’s like a power thing. I mean, science is unfair. It’s really political. A lot of it’s self-promotion and who your mentors are and who’s fighting the fight for you matters. And to be successful in science doesn’t necessarily mean you’re doing good science. It’s doing the repeat things and proving what’s already known is correct. And people who make these quantum leaps often are kind of off to the side. And then all of a sudden, people are like, oh my God, why didn’t I think of that?

But this is probably true of most quantum shifts. I mean, if it wasn’t remarkable, people would have been doing it already.

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FLORA LICHTMAN: This is an interesting paradox of science. Even though the whole profession revolves around the concept that data reigns supreme, that opinions must be overturned by evidence, science is comprised of people who, like people everywhere, have their own horse in the race, their own biases, and blind spots. And on top of that, Kati was no good at playing politics. So even though Kati and Drew solved these problems that ultimately won them the Nobel freaking Prize, at the time, those breakthroughs didn’t do much for Kati’s status in the academic world.

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– Kate had no reputation and was seen kind of as a pariah. And I wouldn’t say she was laughed at, but sort of.

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FLORA LICHTMAN: And I think if I was sort of laughed at for decades, especially when I knew I was right, one of two things might happen to me. One, I’d get bitter as hell. But Kati had some ways of mitigating this.

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– I don’t let anybody get under my skin. And sometimes, when certain people said something, under the table, I put my middle finger up. But then–

[LAUGHING]

– Did you really?

– Yes, but not at the top of the table. And I just release the little immediate stress, and that was it.

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FLORA LICHTMAN: The other risk of being laughed at for so long is getting defeated. It’s hard to keep other people’s doubts from worming their way inside of you, rotting your self-confidence. But the people closest to Kati, the ones who knew her the best, said they didn’t see any sign of this.

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– She’s very tough.

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FLORA LICHTMAN: This is Kati’s daughter, Susan Francia, the gold medal Olympic rower.

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– But it’s interesting. Even when she came home, and that’s the time where you can be vulnerable, I mean, I don’t think I ever really saw my mom cry.

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FLORA LICHTMAN: And to me, this is the most fascinating part of Kati’s story. Most people require a healthy dose of positive affirmation to keep on keeping on. But Kati’s work and her ideas were dismissed for decades, and yet she stayed the course. So besides her scientific insights, what was it about her or her worldview that allowed her to keep betting on herself and her idea?

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– Honestly, I think it’s her personality. My mom was always so good about being solution-oriented. She would just be like, OK, this [BEEP] happened, what’s next? What am I going to do?

– If you want to do something, you find a way. And if you don’t, then you find excuses.

– That’s an aphorism Susan heard a lot over the years.

– Yeah, yeah. Pretty much growing up, that’s all I heard. I mean, when we came to this country, I’m sure she told you, we had, I think $1,000, maybe not even. And anytime I started to go into bratty Susan mode, it was like a very big reminder of, we came to this country with nothing, and we’re going to make everything of it. So it’s on you to take this opportunity and to be the best that you can be.

I think that also helped me a lot in rowing. When it would be like, you end up in the second boat or this or that, and it’s almost like that, I’ll show you attitude.

– I remember when I was demoted. I was 40 years old and demoted at University of Pennsylvania. And then with David help, I get this laboratory. And I loudly say, the bench is here. I am in the United States of America. Where else, if not here, I can do the work? I still can do it. I felt still empowered by that fact that I am here.

– Do you think that being an immigrant made you more resilient?

– Oh yes, I am sure. We arrived here. We had no relatives. I had no teacher– not a classmate. We don’t know the rules. We don’t anybody. We don’t know who to turn to. And many people, if they don’t experience this, they don’t even that they will be able to survive.

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FLORA LICHTMAN: Kati had proved to herself over and over that she could survive. So people raising an eyebrow about her research, that was small potatoes compared to what she went through just to get here. That life experience built her faith in herself.

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– I always believe in myself, and that is what I’m telling everybody else is that you have to believe that with hard work and perseverance, can fulfill your dreams.

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FLORA LICHTMAN: Kati left Penn in 2013 when her stuff was thrown in the garbage can. And while academia was still largely sleeping on Drew and Katie’s work, the pharmaceutical industry had taken note. As Kati was being pushed out, pharma companies were ramping up mRNA therapeutic research programs. Kati took a job at BioNTech. In 2018, they started working on an mRNA flu vaccine with Pfizer. Then 2020 came, and we all know what happened.

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– The breaking news– stay at home. That is the order tonight from four state governors as the coronavirus pandemic spreads.

– We know the hospital surge is coming.

– We’re very worried about every city in the United States.

– Keep getting to these grim milestones, well, yesterday–

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FLORA LICHTMAN: Immediately, BioNTech and the other pharmaceutical companies changed gears.

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– They immediately knew that it is, oh, this is a pandemic. And, oh, 2,000 people work here, now this whole thing is now is making vaccine.

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– Tonight, the first doses of Pfizer’s coronavirus vaccine are on the move.

– It’s the moment so many Americans have been waiting for after such a devastating year that’s taken the lives of nearly 300,000 people across this country.

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FLORA LICHTMAN: It’s astonishing when you trace this moment of COVID vaccine rollout to where it began– to Drew and Kati’s 2005 breakthrough to the decades of gloveless beaker rinses that Kati did before that. And it’s also kind of frightening to think that this world-changing scientific breakthrough relied so much on the extraordinary resilience of one person.

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– My mom and I both talked about this finish line. And in rowing, you’re going backwards. You don’t see the finish line, but you’re going to get there eventually. And you know it’s 2,000 meters. In science, that finish line can get pushed out. It can come in. And then you cross that finish line. You’re like, I had a success– like her breakthrough in 2005. And then you’re like, OK, we did it. We won. And then there’s nobody there to cheer.

And then fast forward, 20 some odd years, and then they’re like, oh, OK, here’s your podium.

– Dear professors Kariko and Weissman, on behalf of the Nobel Assembly at Karolinska Institutet, it’s my great joy and privilege to convey to you our warmest congratulations. I invite you now to step forward to receive the Nobel Prize from the hands of His Majesty the King.

[TRUMPET FANFARE]

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– Did you expect to win a Nobel Prize?

– No. I never even dreamed. They said that every scientist dreams about– I did not.

– How long did it take to feel like reality?

– Not even today. It is just kind of unbelievable for me.

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– When she asked me to go, I started to cry. The joy I felt for her and for the– it was– we all overcome obstacles in our life. And just to see someone that successful, knowing what she went through and knowing where she came from, it’s just a lesson.

– Life is not fair– nowhere. Look around– politics, anything you look. Focus on what is in front of you, what you can change. And then you will have fun.

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FLORA LICHTMAN: The Leap is a production of the Hypothesis Fund. The show is hosted by me, Flora Lichtman, and produced by Annette Heist, editing by Devon Taylor, Pajau Vangay, and David Sanford. Fact checking by Nicole Pasulka. Mixing and scoring by Emma Munger. Music by Joshua Budo Karp. Thank you for listening.

The SciFri pod is back tomorrow with a conversation with a medical sculptor who makes lifelike replicas of body parts for health professionals to train on. And you can catch another episode in this series of The Leap next Monday. Here’s a sneak peek.

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– So, yes, we were on a volcano because we took a calculated risk that we needed to get additional information to tell us when the explosion was going to happen.

– Talk me through the risks of going on to an erupting volcano. What are the risks of that?

[LAUGHING]

– Apart from dying?

– Well, how could you die? Tell me all the ways.

– Well, it’s a very– it’s a really, really bad way.

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FLORA LICHTMAN: You don’t want to miss it. That’s next Monday.